不对称 2,6-双（亚苄基）环己酮：合成、细胞毒性活性和 QSAR 研究。

Asymmetrical 2,6-bis(benzylidene)cyclohexanones: Synthesis, cytotoxic activity and QSAR study.

机构信息

Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Eur J Med Chem. 2012 Apr;50:113-23. doi: 10.1016/j.ejmech.2012.01.045. Epub 2012 Jan 28.

DOI:10.1016/j.ejmech.2012.01.045

Abstract

In order to develop novel anti-cancer agents, a series of asymmetrical 2,6-bis (benzylidene)cyclohexanone derivatives containing nitrobenzylidene moiety were synthesized and their cytotoxic activity were determined in vitro against MDA-MB 231, MCF-7 and SK-N-MC cell lines using MTT assay. Among the tested compounds, the highest activity against MDA-MB 231 cells was achieved by 2-(3-bromo-5-methoxy-4-propoxybenzylidene)-6-(2-nitrobenzylidene)cyclohexanone (compound 5d). Whereas, compound 5j (the 3-nitro analog of compound 5d) was the most potent compound against MCF-7 and SK-N-MC cell lines. The results indicated that the cytotoxic activity profile against different tumor cells can be optimized by desired 4-alkoxy-3-bromo-5-methoxybenzylidene scaffold.

摘要

为了开发新型抗癌药物，我们合成了一系列含有亚硝基苯甲叉部分的不对称 2,6-双（苯亚甲基）环己酮衍生物，并通过 MTT 法测定了它们对 MDA-MB 231、MCF-7 和 SK-N-MC 细胞系的体外细胞毒性。在测试的化合物中，2-(3-溴-5-甲氧基-4-丙氧基苯亚甲基）-6-(2-亚硝基苯亚甲基）环己酮（化合物 5d）对 MDA-MB 231 细胞的活性最高。而化合物 5j（化合物 5d 的 3-硝基类似物）对 MCF-7 和 SK-N-MC 细胞系的活性最强。结果表明，通过所需的 4-烷氧基-3-溴-5-甲氧基苯亚甲基支架可以优化对不同肿瘤细胞的细胞毒性活性谱。